Methods of reducing rhinovirus contagion and related compositions

Abstract

The present invention relates to the use of pleconaril to reduce the contagion of rhinovirus virions shed from a host infected with a rhinovirus and thereby reduce disease transmission or re-infection.

1 . A method of reducing rhinovirus contagion by a host infected with one or more rhinoviruses comprising administering to said host an amount of pleconaril or a salt thereof, which is effective to impart to the nasal mucus excreted by said host a concentration of pleconaril that is sufficient to reduce infectivity of virions shed in said excreted mucus, and thereby render said infected host less rhinovirally contagious when in contact with an uninfected host.  
   
   
       2 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 39, 47, 55, 71, 83, 92, 2, 68, 74, 100, 21, 22, 35, 58, 79, 7, 51, 85, 89, 6, 20, 37, 40, 78, 3, 34, 96, 25, 38, 88, 36, 44, 56, 66, 75, 10, 31, 86, 11, 1B, 14, 33, 46, 62, 63, 49, 57, 80, 90, 28, 19, 24, 61, 73, 9, 82, 17, 30, 43, 18, 76, 67, 29, 53, 70, 81, 23, 64, 32, 65, 50, 12, 1A, 54, 60, 77, 16, 13, 15, 91, 59, 95, 72, 94, 26, 41, 48, 98, 52, 8, 45, 27, and 69.  
   
   
       3 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 39, 47, 55, 71, 83, 92, 2, 68, 74, and 100.  
   
   
       4 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 21, 22, 35, 58, 79, 7, 51, 85, 89, and 6.  
   
   
       5 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 20, 37, 40, 78, 3, 34, 96, 25, 38, and 88.  
   
   
       6 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 36, 44, 56, 66, 75, 10, 31, 86, 11, and 1B.  
   
   
       7 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 14, 33, 46, 62, 63, 49, 57, 80, 90, and 28.  
   
   
       8 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 19, 24, 61, 73, 9, 82, 17, 30, 43, and 18.  
   
   
       9 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 76, 67, 29, 53, 70, 81, 23, 64, 32, and 65.  
   
   
       10 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 50, 12, 1A, 54, 60, 77, 16, 13, 15, and 91.  
   
   
       11 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 59, 95, 72, 94, 26, 41, 48, 98, 52, and 8.  
   
   
       12 . A method according to  claim 1 , wherein the shed virions include at least one rhinovirus serotype selected from the group consisting of 45, 27, and 69.  
   
   
       13 . A method according to  claim 1  wherein said virions are progeny virions.  
   
   
       14 . The method according to  claim 1  wherein the infectivity of the progeny virions shed in nasal mucus excreted from said host is reduced to the extent that there is no corresponding cultureable rhinovirus in a sample of nasal mucus taken from said host within 1 to 10 hours after administering said infectivity reducing amount of pleconaril.  
   
   
       15 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about the 50 percent minimum inhibitory concentration.  
   
   
       16 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about the 75 percent minimum inhibitory concentration.  
   
   
       17 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about the 90 percent minimum inhibitory concentration.  
   
   
       18 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about the 95 percent minimum inhibitory concentration.  
   
   
       19 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about the 99% minimum inhibitory concentration.  
   
   
       20 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about 0.2 μM.  
   
   
       21 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about 4.3 μM.  
   
   
       22 . The method according to  claim 1 , wherein said nasal mucus has a pleconaril nasal mucus concentration of at least about 12.5 μM.  
   
   
       23 . The method according to  claim 1 , wherein said pleconaril nasal mucus concentration is less than about 12.5 μM.  
   
   
       24 . The method according to  claim 1 , wherein said pleconaril nasal mucus concentration is less than about 4.3 μM.  
   
   
       25 . The method according to  claim 1 , wherein said pleconaril is administer by inhalation.  
   
   
       26 . The method according to  claim 1 , wherein said pleconaril is administer topically.  
   
   
       27 . A method of protecting an un-infected host from rhinovirus infection due to contagion by a rhinovirus-infected host comprising administering to said infected host an infectivity reducing amount of pleconaril, wherein said infected host: 
 a) is shedding virions of at least one rhinovirus serotype selected from the group consisting of 39, 47, 55, 71, 83, 92, 2, 68, 74, 100, 21, 22, 35, 58, 79, 7, 51, 85, 89, 6, 20, 37, 40, 78, 3, 34, 96, 25, 38, 88, 36, 44, 56, 66, 75, 10, 31, 86, 11, 1B, 14, 33, 46, 62, 63, 49, 57, 80, 90, 28, 19, 24, 61, 73, 9, 82, 17, 30, 43, 18, 76, 67, 29, 53, 70, 81, 23, 64, 32, 65, 50, 12, 1A, 54, 60, 77, 16, 13, 15, 91, 59, 95, 72, 94, 26, 41, 48, 98, 52, 8, 45, 27, and 69, and    b) is exposed to said un-infected host,    wherein pleconaril is administered during a time period from about 1 to about 10 hours before said exposure.    
   
   
       28 . The method according to  claim 27 , wherein the period of administration is from about 2 to about 4 hours.  
   
   
       29 . The method according to  claim 27 , wherein the virions are progeny virions.  
   
   
       30 . A method of protecting an un-infected host from rhinovirus infection due to contagion by a rhinovirus-infected host comprising administering an infectivity reducing amount of pleconaril to said un-infected host, wherein pleconaril is administered during the time period of about 1 to about 10 hours before the prospective contact between the uninfected host and virions of at least one rhinovirus serotype selected from the group consisting of 39, 47, 55, 71, 83, 92, 2, 68, 74, 100, 21, 22, 35, 58, 79, 7, 51, 85, 89, 6, 20, 37, 40, 78, 3, 34, 96, 25, 38, 88, 36, 44, 56, 66, 75, 10, 31, 86, 11, 1B, 14, 33, 46, 62, 63, 49, 57, 80, 90, 28, 19, 24, 61, 73, 9, 82, 17, 30, 43, 18, 76, 67, 29, 53, 70, 81, 23, 64, 32, 65, 50, 12, 1A, 54, 60, 77, 16, 13, 15, 91, 59, 95, 72, 94, 26, 41, 48, 98, 52, 8, 45, 27, and 69.  
   
   
       31 . A method of inhibiting contagion of VRI by an infected host to an un-infected host comprising reducing the infectivity of progeny rhinovirus virions that are shed from an infected host by administering to said infected host an infectivity reducing amount of pleconaril or a salt thereof.  
   
   
       32 . A method of reducing the risk of transmitting VRI from an infected host infected with a rhinovirus to an un-infected host not infected with a rhinovirus, comprising administering to said infected host an infectivity reducing amount of pleconaril or a salt thereof.  
   
   
       33 . A method according to  claim 32 , wherein there is a 50 percent or greater risk of said infected host transmitting a VRI to said un-infected host before administration of pleconaril.  
   
   
       34 . A method according to  claim 33 , wherein said risk is greater than 75 percent.  
   
   
       35 . A method according to  claim 33 , wherein said risk is greater than 95 percent.  
   
   
       36 . A method according to  claim 33 , wherein said risk is greater than 99 percent.  
   
   
       37 . A method of inhibiting contagion of VRI in an uninfected host, comprising administering an infectivity reducing amount of pleconaril or a salt thereof to an infected patient infected with one or more rhinoviruses before said uninfected host is exposed to said infected patient.  
   
   
       38 . A method according to  claim 37 , wherein said infectivity reducing amount of pleconaril is administered during a time period from about 1 to about 10 hours before said uninfected host is exposed to said infected patient.  
   
   
       39 . A method according to  claim 38 , wherein the period of administration is from about 2 to about 4 hours.  
   
   
       40 . A method of reducing the infectivity of nasal mucus comprising treating mucus containing one or more rhinoviruses with an infectivity reducing amount of pleconaril or a salt thereof.  
   
   
       41 . A method of reducing nasal mucus infectivity according to  claim 40 , wherein said pleconaril is derived from oral administration of pleconaril to a host.  
   
   
       42 . A method of reducing nasal mucus infectivity according to  claim 40 , wherein said pleconaril is not derived from: 
 a) nasal administration of a pleconaril formulation, or    b) exogenous combination of nasal mucus and pleconaril.    
   
   
       43 . A method of reducing according to  claim 40 , wherein said pleconaril is derived from tissues impregnated with a pleconaril composition and said tissues are used to collect excreted nasal mucus.  
   
   
       44 . A method according to  claim 37 , wherein said pleconaril is administered orally.  
   
   
       45 . A method according to  claim 44 , wherein said infectivity reducing amount of pleconaril is 400 mg three times daily for 5 days.  
   
   
       46 . A method according to  claim 45 , wherein said pleconaril is administered in capsule form.  
   
   
       47 . A method according to  claim 45  wherein said pleconaril is administered as a tablet.  
   
   
       48 . A method according to  claim 47 , wherein said tablet comprises 200 mg of pleconaril, and the following inactive ingredients: lactose, starch, crospovidone, sodium lauryl sulfate, colloidal silicon dioxide, and magnesium stearate.  
   
   
       49 . A composition comprising human nasal mucus and pleconaril.  
   
   
       50 . A composition according to  claim 49 , wherein said pleconaril is derived as a component from nasal epithial cell excretion.  
   
   
       51 . The composition according to  claim 49 , additionally comprising one or more metabolites of pleconaril.  
   
   
       52 . The composition according to  claim 49 , additionally comprising one or more rhinoviruses.  
   
   
       53 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 39, 47, 55, 71, 83, 92, 2, 68, 74, 100, 21, 22, 35, 58, 79, 7, 51, 85, 89, 6, 20, 37, 40, 78, 3, 34, 96, 25, 38, 88, 36, 44, 56, 66, 75, 10, 31, 86, 11, 1B, 14, 33, 46, 62, 63, 49, 57, 80, 90, 28, 19, 24, 61, 73, 9, 82, 17, 30, 43, 18, 76, 67, 29, 53, 70, 81, 23, 64, 32, 65, 50, 12, 1A, 54, 60, 77, 16, 13, 15, 91, 59, 95, 72, 94, 26, 41, 48, 98, 52, 8, 45, 27, and 69.  
   
   
       54 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 39, 47, 55, 71, 83, 92, 2, 68, 74, and 100.  
   
   
       55 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 21, 22, 35, 58, 79, 7, 51, 85, 89, and 6.  
   
   
       56 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 20, 37, 40, 78, 3, 34, 96, 25, 38, and 88.  
   
   
       57 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 36, 44, 56, 66, 75, 10, 31, 86, 11, and 1B.  
   
   
       58 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 14, 33, 46, 62, 63, 49, 57, 80, 90, and 28.  
   
   
       59 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 19, 24, 61, 73, 9, 82, 17, 30, 43, and 18.  
   
   
       60 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 76, 67, 29, 53, 70, 81, 23, 64, 32, and 65.  
   
   
       61 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 50, 12, 1A, 54, 60, 77, 16, 13, 15, and 91.  
   
   
       62 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 59, 95, 72, 94, 26, 41, 48, 98, 52, and 8.  
   
   
       63 . The composition according to  claim 49 , wherein said rhinoviruses is at least one selected from the group consisting of serotype 45, 27, and 69.  
   
   
       64 . A composition comprising human nasal mucus and pleconaril, wherein said pleconaril is not derived from exogenous nasal administration.